Recent studies by other groups have demonstrated that the extracellular matrix confers much more than a type of extracellular support or cement and in fact plays an important role in the control of cell growth, differentiation and migration. Attachment of cells to matrix and invasion of cells into matrix, (including malignant metastases) varies with the type of matrix. One type of matrix gel has been shown to promote a differentiated phenotype in a variety of cells. The gel is extracted from the abundant extracellular matrix of the EHS tumor. We hoped that this gel extract could prevent the differentiation of cultured smooth muscle cells which prevents their contractile properties from being studied in vitro. We found that passaged rat aortic smooth muscle cells attached much faster on the gel and on plastic and that in 10% fetal calf serum the cells on matrix grew faster when matrix was added to postconfluent serum starved cells. However, while the matrix supported these cells in the period of starvation, it also blunted the growth response to refeeding the cells with serum. By light microscopy the cells were seen to pick up before reaching confluence, but individually the cells were indistinguishable by electron microscopy from cells grown on plastic. Nor was a voltage dependent calcium channel induced by growing the cells on a gel, as indicated by the fura-2 signal in response to depolarization of potassium. Thusfar, we can only conclude that the gel extract exerts biphasic effects on growth as well as some phenotypic alterations, but does not confer a more differentiated type of electrophysiological response.